Pharmacogenomics—Drug disposition, drug targets, and side effects¶
Evans, W. E., & McLeod, H. L. (2003). Pharmacogenomics—Drug disposition, drug targets, and side effects. New England Journal of Medicine, 348(6), 538-549.
Cited by¶
1 citation across 1 artifact.
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Primes¶
- Therapeutic Window
- Treating the window [MED, MTD] as a sharp boundary (below MED is useless, above MTD is toxic, within is safe) ignores the gradualness of dose-response curves and the substantial inter-individual variability—variability which Evans and McLeod (2003) document is often largely genetic, with polymorphisms in drug-metabolism enzymes shifting individual windows by an order of magnitude.
This sourceFoundational pharmacogenomics review: documents how genetic polymorphisms in drug-metabolism enzymes (CYP2C9, CYP2D6, TPMT, UGT1A1) and drug targets shift individual therapeutic windows substantially, undermining naive use of population-mean MED/MTD point estimates.
- Treating the window [MED, MTD] as a sharp boundary (below MED is useless, above MTD is toxic, within is safe) ignores the gradualness of dose-response curves and the substantial inter-individual variability—variability which Evans and McLeod (2003) document is often largely genetic, with polymorphisms in drug-metabolism enzymes shifting individual windows by an order of magnitude.
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